Does hormonal manipulation in conjunction with permanent interstitial brachytherapy, with or without supplemental external beam irradiation, improve the biochemical outcome for men with intermediate or high-risk prostate cancer?

To determine whether hormonal manipulation improves the biochemical outcome for men with intermediate or high-risk prostate cancer and undergoing permanent brachytherapy with or without supplemental external beam radiation therapy. From April 1995 to August 2000, 350 patients with intermediate-risk (225 men; a Gleason score of greater than or equal to 7 or a prostate specific antigen, PSA, level of greater than or equal to 10 ng/mL or clinical stage greater than or equal to T2b) or high-risk features (125 men; two or three of a Gleason score of greater than or equal to 7 or PSA greater than or equal to 10 ng/mL or clinical stage greater than or equal to T2b) underwent transperineal ultrasonography-guided permanent brachytherapy. No patient underwent pathological lymph node staging. Of these patients, 293 received supplemental external beam radiation therapy (EBRT), 141 received hormonal manipulation, with 82 having hormonal therapy for less than or equal to 4 months (median 4) for cytoreduction, while 59 had neoadjuvant and adjuvant hormonal manipulation (median 8 and 12 months for intermediate- and high-risk, respectively). The median patient age was 68.5 years. No patient was lost to follow-up. The mean (sd) and median follow-up was 50 (18) and 49 months (calculated from the day of implantation). Biochemical disease-free (BDF) survival was defined using a consensus definition. The clinical variables evaluated for BDF survival included risk group, Gleason score, patient age, clinical T-stage and pretreatment PSA. Treatment variables included use of hormonal manipulation stratified into cytoreductive (less than or equal to 4 months) vs adjuvant (> 4 months) regimens, supplemental EBRT, isotope and dosimetric variables. For intermediate-risk patients, the 6-year actuarial BDF survival rates were 98%, 96% and 100% for hormone naive, cytoreductive and adjuvant treatment, respectively (P = 0.693); for high-risk patients the respective values were 79%, 94% and 92% (P = 0.046). When stratified by pretreatment PSA, hormonal manipulation improved the outcome for patients with a PSA of greater than or equal to 10 ng/mL (P = 0.019), but not for those with < 10 ng/mL (P = 0.661). Hormonal status was not statistically significant in predicting biochemical outcome when stratified by Gleason score. The follow-up in hormone-naive patients was significantly longer than that in hormonally manipulated patients, at 55 (20) vs 43 (15) months (P < 0.001). In a multivariate analysis only the Gleason score predicted failure in intermediate-risk patients, while pretreatment PSA, the use of hormonal manipulation and Gleason score predicted the outcome in high-risk patients (P = 0.035). For both hormone-naive and hormonally manipulated BDF patients, the median PSA level after implantation was < 0.1 ng/mL. In patients treated by permanent prostate brachytherapy, hormonal manipulation improved the biochemical outcome for those at high-risk and those with an initial PSA of >= 10 ng/mL, but not for those with intermediate-risk features. The use of hormonal therapy for > 4 months conferred no additional biochemical advantage over short-course regimens. Because the follow-up in hormone-naive patients was longer than that for those receiving hormonal manipulation, additional follow-up will be mandatory to confirm the durability of these findings.